Purpose: Metabolic diseases such as diabetes mellitus may play a role in the development and progression of prostate cancer (PC); however, this association remains to be explored in the context of specific PC stages. The objective of this study was to systematically review the evidence for an association between diabetes and overall, early, or advanced PC risk. Materials and Methods: A systematic review with meta-analysis was performed (MEDLINE, EMBASE, and CINAHL) from inception until September 2023. Cohort and case-control studies that assessed PC risk in adult males (≥18 years) associated with type 2 diabetes mellitus or diabetes (if there was no distinction between diabetes type) were included. The Newcastle-Ottawa Scale (NOS) was used to assess study bias; those with NOS<7 were excluded. Evidence certainty was assessed with the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) method. Results: Thirty-four studies (n=26 cohorts and n=8 case-controls) were included. Of these, 32 assessed diabetes and all PC stages combined, 12 included early PC stages, and 15 included advanced PC stages. Our meta-analysis showed diabetes had a protective effect against early PC development (n=11, risk ratio [RR]=0.71; 95% confidence interval [CI]=0.61–0.83, I2=84%) but no association was found for combined (n=21, RR=0.95; 95% CI=0.79–1.13, I2=99%) or advanced PC stages (n=15, RR=0.96; 95% CI=0.77–1.18, I2=98%) at diagnosis. According to GRADE, the evidence certainty was very low. Conclusions Diabetes may be protective against early PC stages, yet evidence linking diabetes to risk across all stages, and advanced PC specifically, is less conclusive. High heterogeneity may partially explain discrepancy in findings and was mostly associated with study design, method used for PC diagnosis, and risk measures. Our results may aid risk stratification of males with diabetes and inform new approaches for PC screening in this group, especially considering the reduced sensitivity of prostate-specific antigen values for those with diabetes.

The International Severe Asthma Registry (ISAR) was established in 2017 to advance the understanding of severe asthma and its management, thereby improving patient care worldwide. As the first global registry for adults with severe asthma, ISAR enabled individual registries to standardize and pool their data, creating a comprehensive, harmonized dataset with sufficient statistical power to address key research questions and knowledge gaps. Today, ISAR is the largest repository of real-world data on severe asthma, curating data on nearly 35,000 patients from 28 countries worldwide, and has become a leading contributor to severe asthma research. Research using ISAR data has provided valuable insights on the characteristics of severe asthma, its burdens and risk factors, real-world treatment effectiveness, and barriers to specialist care, which are collectively informing improved asthma management. Besides changing clinical thinking via research, ISAR aims to advance real-world practice through initiatives that improve registry data quality and severe asthma care. In 2024, ISAR refined essential research variables to enhance data quality and launched a web-based data acquisition and reporting system (QISAR), which integrates data collection with clinical consultations and enables longitudinal data tracking at patient, center, and population levels. Quality improvement priorities include collecting standardized data during consultations and tracking and optimizing patient journeys via QISAR and integrating primary/secondary care pathways to expedite specialist severe asthma management and facilitate clinical trial recruitment. ISAR envisions a future in which timely specialist referral and initiation of biologic therapy can obviate long-term systemic corticosteroid use and enable more patients to achieve remission.

Purpose: Metabolic diseases such as diabetes mellitus may play a role in the development and progression of prostate cancer (PC); however, this association remains to be explored in the context of specific PC stages. The objective of this study was to systematically review the evidence for an association between diabetes and overall, early, or advanced PC risk. Materials and Methods: A systematic review with meta-analysis was performed (MEDLINE, EMBASE, and CINAHL) from inception until September 2023. Cohort and case-control studies that assessed PC risk in adult males (≥18 years) associated with type 2 diabetes mellitus or diabetes (if there was no distinction between diabetes type) were included. The Newcastle-Ottawa Scale (NOS) was used to assess study bias; those with NOS<7 were excluded. Evidence certainty was assessed with the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) method. Results: Thirty-four studies (n=26 cohorts and n=8 case-controls) were included. Of these, 32 assessed diabetes and all PC stages combined, 12 included early PC stages, and 15 included advanced PC stages. Our meta-analysis showed diabetes had a protective effect against early PC development (n=11, risk ratio [RR]=0.71; 95% confidence interval [CI]=0.61–0.83, I2=84%) but no association was found for combined (n=21, RR=0.95; 95% CI=0.79–1.13, I2=99%) or advanced PC stages (n=15, RR=0.96; 95% CI=0.77–1.18, I2=98%) at diagnosis. According to GRADE, the evidence certainty was very low. Conclusions Diabetes may be protective against early PC stages, yet evidence linking diabetes to risk across all stages, and advanced PC specifically, is less conclusive. High heterogeneity may partially explain discrepancy in findings and was mostly associated with study design, method used for PC diagnosis, and risk measures. Our results may aid risk stratification of males with diabetes and inform new approaches for PC screening in this group, especially considering the reduced sensitivity of prostate-specific antigen values for those with diabetes.

The International Severe Asthma Registry (ISAR) was established in 2017 to advance the understanding of severe asthma and its management, thereby improving patient care worldwide. As the first global registry for adults with severe asthma, ISAR enabled individual registries to standardize and pool their data, creating a comprehensive, harmonized dataset with sufficient statistical power to address key research questions and knowledge gaps. Today, ISAR is the largest repository of real-world data on severe asthma, curating data on nearly 35,000 patients from 28 countries worldwide, and has become a leading contributor to severe asthma research. Research using ISAR data has provided valuable insights on the characteristics of severe asthma, its burdens and risk factors, real-world treatment effectiveness, and barriers to specialist care, which are collectively informing improved asthma management. Besides changing clinical thinking via research, ISAR aims to advance real-world practice through initiatives that improve registry data quality and severe asthma care. In 2024, ISAR refined essential research variables to enhance data quality and launched a web-based data acquisition and reporting system (QISAR), which integrates data collection with clinical consultations and enables longitudinal data tracking at patient, center, and population levels. Quality improvement priorities include collecting standardized data during consultations and tracking and optimizing patient journeys via QISAR and integrating primary/secondary care pathways to expedite specialist severe asthma management and facilitate clinical trial recruitment. ISAR envisions a future in which timely specialist referral and initiation of biologic therapy can obviate long-term systemic corticosteroid use and enable more patients to achieve remission.

Purpose: Metabolic diseases such as diabetes mellitus may play a role in the development and progression of prostate cancer (PC); however, this association remains to be explored in the context of specific PC stages. The objective of this study was to systematically review the evidence for an association between diabetes and overall, early, or advanced PC risk. Materials and Methods: A systematic review with meta-analysis was performed (MEDLINE, EMBASE, and CINAHL) from inception until September 2023. Cohort and case-control studies that assessed PC risk in adult males (≥18 years) associated with type 2 diabetes mellitus or diabetes (if there was no distinction between diabetes type) were included. The Newcastle-Ottawa Scale (NOS) was used to assess study bias; those with NOS<7 were excluded. Evidence certainty was assessed with the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) method. Results: Thirty-four studies (n=26 cohorts and n=8 case-controls) were included. Of these, 32 assessed diabetes and all PC stages combined, 12 included early PC stages, and 15 included advanced PC stages. Our meta-analysis showed diabetes had a protective effect against early PC development (n=11, risk ratio [RR]=0.71; 95% confidence interval [CI]=0.61–0.83, I2=84%) but no association was found for combined (n=21, RR=0.95; 95% CI=0.79–1.13, I2=99%) or advanced PC stages (n=15, RR=0.96; 95% CI=0.77–1.18, I2=98%) at diagnosis. According to GRADE, the evidence certainty was very low. Conclusions Diabetes may be protective against early PC stages, yet evidence linking diabetes to risk across all stages, and advanced PC specifically, is less conclusive. High heterogeneity may partially explain discrepancy in findings and was mostly associated with study design, method used for PC diagnosis, and risk measures. Our results may aid risk stratification of males with diabetes and inform new approaches for PC screening in this group, especially considering the reduced sensitivity of prostate-specific antigen values for those with diabetes.

The International Severe Asthma Registry (ISAR) was established in 2017 to advance the understanding of severe asthma and its management, thereby improving patient care worldwide. As the first global registry for adults with severe asthma, ISAR enabled individual registries to standardize and pool their data, creating a comprehensive, harmonized dataset with sufficient statistical power to address key research questions and knowledge gaps. Today, ISAR is the largest repository of real-world data on severe asthma, curating data on nearly 35,000 patients from 28 countries worldwide, and has become a leading contributor to severe asthma research. Research using ISAR data has provided valuable insights on the characteristics of severe asthma, its burdens and risk factors, real-world treatment effectiveness, and barriers to specialist care, which are collectively informing improved asthma management. Besides changing clinical thinking via research, ISAR aims to advance real-world practice through initiatives that improve registry data quality and severe asthma care. In 2024, ISAR refined essential research variables to enhance data quality and launched a web-based data acquisition and reporting system (QISAR), which integrates data collection with clinical consultations and enables longitudinal data tracking at patient, center, and population levels. Quality improvement priorities include collecting standardized data during consultations and tracking and optimizing patient journeys via QISAR and integrating primary/secondary care pathways to expedite specialist severe asthma management and facilitate clinical trial recruitment. ISAR envisions a future in which timely specialist referral and initiation of biologic therapy can obviate long-term systemic corticosteroid use and enable more patients to achieve remission.

Objective: In ovarian cancer (OvCa), tumor cell high glucocorticoid receptor (GR) has been associated with poor patient prognosis. In vitro, GR activation inhibits chemotherapyinduced OvCa cell death in association with transcriptional upregulation of genes encoding anti-apoptotic proteins. A recent randomized phase II study demonstrated improvement in progression-free survival (PFS) for heavily pre-treated OvCa patients randomized to receive therapy with a selective GR modulator (SGRM) plus chemotherapy compared to chemotherapy alone. We hypothesized that SGRM therapy would improve carboplatin response in OvCa patient-derived xenograft (PDX). Methods: Six high-grade serous (HGS) OvCa PDX models expressing GR mRNA (NR3C1) and protein were treated with chemotherapy +/− SGRM. Tumor size was measured longitudinally by peritoneal transcutaneous ultrasonography. Results: One of the 6 GR-positive PDX models showed a significant improvement in PFS with the addition of a SGRM. Interestingly, the single model with an improved PFS was least carboplatin sensitive. Possible explanations for the modest SGRM activity include the high carboplatin sensitivity of 5 of the PDX tumors and the potential that SGRMs activate the tumor invasive immune cells in patients (absent from immunocompromised mice). The level of tumor GR protein expression alone appears insufficient for predicting SGRM response. Conclusion The significant improvement in PFS shown in 1 of the 6 models after treatment with a SGRM plus chemotherapy underscores the need to determine predictive biomarkers for SGRM therapy in HGS OvCa and to better identify patient subgroups that are most likely to benefit from adding GR modulation to chemotherapy.

Objective: In ovarian cancer (OvCa), tumor cell high glucocorticoid receptor (GR) has been associated with poor patient prognosis. In vitro, GR activation inhibits chemotherapyinduced OvCa cell death in association with transcriptional upregulation of genes encoding anti-apoptotic proteins. A recent randomized phase II study demonstrated improvement in progression-free survival (PFS) for heavily pre-treated OvCa patients randomized to receive therapy with a selective GR modulator (SGRM) plus chemotherapy compared to chemotherapy alone. We hypothesized that SGRM therapy would improve carboplatin response in OvCa patient-derived xenograft (PDX). Methods: Six high-grade serous (HGS) OvCa PDX models expressing GR mRNA (NR3C1) and protein were treated with chemotherapy +/− SGRM. Tumor size was measured longitudinally by peritoneal transcutaneous ultrasonography. Results: One of the 6 GR-positive PDX models showed a significant improvement in PFS with the addition of a SGRM. Interestingly, the single model with an improved PFS was least carboplatin sensitive. Possible explanations for the modest SGRM activity include the high carboplatin sensitivity of 5 of the PDX tumors and the potential that SGRMs activate the tumor invasive immune cells in patients (absent from immunocompromised mice). The level of tumor GR protein expression alone appears insufficient for predicting SGRM response. Conclusion The significant improvement in PFS shown in 1 of the 6 models after treatment with a SGRM plus chemotherapy underscores the need to determine predictive biomarkers for SGRM therapy in HGS OvCa and to better identify patient subgroups that are most likely to benefit from adding GR modulation to chemotherapy.

Purpose: Metabolic diseases such as diabetes mellitus may play a role in the development and progression of prostate cancer (PC); however, this association remains to be explored in the context of specific PC stages. The objective of this study was to systematically review the evidence for an association between diabetes and overall, early, or advanced PC risk. Materials and Methods: A systematic review with meta-analysis was performed (MEDLINE, EMBASE, and CINAHL) from inception until September 2023. Cohort and case-control studies that assessed PC risk in adult males (≥18 years) associated with type 2 diabetes mellitus or diabetes (if there was no distinction between diabetes type) were included. The Newcastle-Ottawa Scale (NOS) was used to assess study bias; those with NOS<7 were excluded. Evidence certainty was assessed with the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) method. Results: Thirty-four studies (n=26 cohorts and n=8 case-controls) were included. Of these, 32 assessed diabetes and all PC stages combined, 12 included early PC stages, and 15 included advanced PC stages. Our meta-analysis showed diabetes had a protective effect against early PC development (n=11, risk ratio [RR]=0.71; 95% confidence interval [CI]=0.61–0.83, I2=84%) but no association was found for combined (n=21, RR=0.95; 95% CI=0.79–1.13, I2=99%) or advanced PC stages (n=15, RR=0.96; 95% CI=0.77–1.18, I2=98%) at diagnosis. According to GRADE, the evidence certainty was very low. Conclusions Diabetes may be protective against early PC stages, yet evidence linking diabetes to risk across all stages, and advanced PC specifically, is less conclusive. High heterogeneity may partially explain discrepancy in findings and was mostly associated with study design, method used for PC diagnosis, and risk measures. Our results may aid risk stratification of males with diabetes and inform new approaches for PC screening in this group, especially considering the reduced sensitivity of prostate-specific antigen values for those with diabetes.

The International Severe Asthma Registry (ISAR) was established in 2017 to advance the understanding of severe asthma and its management, thereby improving patient care worldwide. As the first global registry for adults with severe asthma, ISAR enabled individual registries to standardize and pool their data, creating a comprehensive, harmonized dataset with sufficient statistical power to address key research questions and knowledge gaps. Today, ISAR is the largest repository of real-world data on severe asthma, curating data on nearly 35,000 patients from 28 countries worldwide, and has become a leading contributor to severe asthma research. Research using ISAR data has provided valuable insights on the characteristics of severe asthma, its burdens and risk factors, real-world treatment effectiveness, and barriers to specialist care, which are collectively informing improved asthma management. Besides changing clinical thinking via research, ISAR aims to advance real-world practice through initiatives that improve registry data quality and severe asthma care. In 2024, ISAR refined essential research variables to enhance data quality and launched a web-based data acquisition and reporting system (QISAR), which integrates data collection with clinical consultations and enables longitudinal data tracking at patient, center, and population levels. Quality improvement priorities include collecting standardized data during consultations and tracking and optimizing patient journeys via QISAR and integrating primary/secondary care pathways to expedite specialist severe asthma management and facilitate clinical trial recruitment. ISAR envisions a future in which timely specialist referral and initiation of biologic therapy can obviate long-term systemic corticosteroid use and enable more patients to achieve remission.